Current standard cancer therapies include surgery, chemotherapy, radiation, and autologous cell transplantation. Surgery is generally effective in the early treatment of cancer; however, metastatic growth of tumors can prevent any complete cure. Chemotherapy, which involves administration of compounds having antitumor activity, while effective in the treatment of some cancers, is often accompanied by severe side effects, including nausea and vomiting, bone marrow depression, renal damage, and central nervous system depression. Radiation therapy has also been used to target cancer cells, as cancer cells are less able to repair themselves after treatment with radiation. However, radiation cannot be used to treat many cancers because of the sensitivity of normal cells which surround cancerous tissue.
Efforts to improve the efficacy of standard cancer therapies by combining them have been moderately successful. Multi-drug combination chemotherapy regimens and high dose therapy have improved the outlook of patients with certain types of cancer, e.g., intermediate-grade histology non-Hodgkin's lymphoma (NHL), particularly when followed by autologous stem cell rescue. However, no therapeutic options have been proven to be of benefit to patients who have active disease after transplantation.
The goal of many recent research efforts has been to specifically target cancer cells with suicide or toxic genes (“therapeutic genes”) and techniques to transfer therapeutic genes into tumor cells have been developed (Freeman, et al. 1996). However, to date these techniques have been hampered by the restricted range of action of the therapeutic genes as cell killing is predominantly limited to transduced cells (Paillard, 1997). This problem is exacerbated by the fact that levels of transduction with available gene delivery vectors are low, even in vitro.
Lytic viruses with tissue tropisms can have anti-cancer effects when the natural tissue targets of these viruses include cancer cells. Anecdotal accounts of regression of Hodgkin's disease and of Non-Hodgkin's Lymphoma (NHL) after natural measles virus infection have been reported in the literature (Taqi, et al., 1991; Bluming and Ziegler, 1971). A study in which another paramyxovirus, mumps, was administered to 90 patients with advanced malignancy was reported by Asada (1974). In this study, a tissue culture suspension of wild-type mumps virus, was administered by a variety of routes, mostly to patients suffering from advanced and terminal cancer. Almost half of the patients had significant, although short-lived responses in treated regions. Newcastle Disease Virus, an avian paramyxovirus has also shown promising results in preclinical studies (Lorence, et al. 1994; Lorence, et a1.1988; Reichard, et al. 1992); however, humans lack any natural immunity to the virus, discouraging its widespread use in humans.